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Review ArticleReview

Development of targeted therapies in treatment of glioblastoma

Yuan-Yuan Xu, Pei Gao, Ying Sun and You-Rong Duan
Cancer Biology & Medicine September 2015, 12 (3) 223-237; DOI: https://doi.org/10.7497/j.issn.2095-3941.2015.0020
Yuan-Yuan Xu
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
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Pei Gao
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
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Ying Sun
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
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You-Rong Duan
1State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200032, China
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  • For correspondence: yrduan{at}shsci.org
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References

  1. 1.↵
    1. Ostrom QT,
    2. Gittleman H,
    3. Liao P,
    4. Rouse C,
    5. Chen Y,
    6. Dowling J, et al.
    CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2007-2011. Neuro Oncol 2014;16:iv1–iv63.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Louis DN,
    2. Ohgaki H,
    3. Wiestler OD,
    4. Cavenee WK,
    5. Burger PC,
    6. Jouvet A, et al.
    The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007;114:97–109.
    OpenUrlCrossRefPubMedWeb of Science
  3. 3.↵
    1. Ohgaki H,
    2. Kleihues P.
    Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol 2005;64:479–489.
    OpenUrlCrossRefPubMed
  4. 4.
    1. Arora RS,
    2. Alston RD,
    3. Eden TO,
    4. Estlin EJ,
    5. Moran A,
    6. Birch JM.
    Age–incidence patterns of primary CNS tumors in children, adolescents, and adults in England. Neuro Oncol 2009;11:403–413.
    OpenUrlCrossRefPubMed
  5. 5.
    1. Lee CH,
    2. Jung KW,
    3. Yoo H,
    4. Park S,
    5. Lee SH.
    Epidemiology of primary brain and central nervous system tumors in Korea. J Korean Neurosurg Soc 2010;48:145–152.
    OpenUrlCrossRefPubMed
  6. 6.
    1. Dobes M,
    2. Khurana VG,
    3. Shadbolt B,
    4. Jain S,
    5. Smith SF,
    6. Smee R, et al.
    Increasing incidence of glioblastoma multiforme and meningioma, and decreasing incidence of Schwannoma (2000-2008): findings of a multicenter Australian study. Surg Neurol Int 2011;2:176.
    OpenUrlCrossRefPubMed
  7. 7.↵
    1. Gigineishvili D,
    2. Shengelia N,
    3. Shalashvili G,
    4. Rohrmann S,
    5. Tsiskaridze A,
    6. Shakarishvili R.
    Primary brain tumour epidemiology in Georgia: first-year results of a population-based study. J Neurooncol 2013;112:241–246.
    OpenUrlCrossRefPubMed
  8. 8.↵
    1. Dunn GP,
    2. Rinne ML,
    3. Wykosky J,
    4. Genovese G,
    5. Quayle SN,
    6. Dunn IF, et al.
    Emerging insights into the molecular and cellular basis of glioblastoma. Genes Dev 2012;26:756–784.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Network NCC.
    NCCN Clinical Practice Guidelines in Oncology: Central Nervous System Cancers. Version 2. 2014.
  10. 10.↵
    1. Stupp R,
    2. Mason WP,
    3. Van Den Bent MJ,
    4. Weller M,
    5. Fisher B,
    6. Taphoorn MJ, et al.
    Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.
    OpenUrlCrossRefPubMedWeb of Science
  11. 11.↵
    1. Wen PY,
    2. Kesari S.
    Malignant gliomas in adults. N Engl J Med 2008;359:492–507.
    OpenUrlCrossRefPubMedWeb of Science
  12. 12.↵
    1. Wallner KE,
    2. Galicich JH,
    3. Krol G,
    4. Arbit E,
    5. Malkin MG.
    Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma. Int J Radiat Oncol Biol Phys 1989;16:1405–1409.
    OpenUrlCrossRefPubMedWeb of Science
  13. 13.↵
    1. Serwer LP,
    2. James CD.
    Challenges in drug delivery to tumors of the central nervous system: an overview of pharmacological and surgical considerations. Adv Drug Deliv Rev 2012;64:590–597.
    OpenUrlCrossRefPubMed
  14. 14.
    1. Gao H,
    2. Jiang X.
    Progress on the diagnosis and evaluation of brain tumors. Cancer Imaging 2013;13:466–481.
    OpenUrlCrossRef
  15. 15.↵
    1. Gao H,
    2. Pang Z,
    3. Jiang X.
    Targeted delivery of nano-therapeutics for major disorders of the central nervous system. Pharm Res 2013;30:2485–2498.
    OpenUrlPubMed
  16. 16.↵
    1. Zhan C,
    2. Wei X,
    3. Qian J,
    4. Feng L,
    5. Zhu J,
    6. Lu W.
    Co-delivery of TRAIL gene enhances the anti-glioblastoma effect of paclitaxel in vitro and in vivo. J Control Release 2012;160:630–636.
    OpenUrlCrossRefPubMed
  17. 17.
    1. Sarin H,
    2. Kanevsky AS,
    3. Wu H,
    4. Sousa AA,
    5. Wilson CM,
    6. Aronova MA, et al.
    Physiologic upper limit of pore size in the blood-tumor barrier of malignant solid tumors. J Transl Med 2009;7:51.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Groothuis DR.
    The blood-brain and blood-tumor barriers: a review of strategies for increasing drug delivery. Neuro Oncol 2000;2:45–59.
    OpenUrlCrossRefPubMedWeb of Science
  19. 19.↵
    1. Jones AR,
    2. Shusta EV.
    Blood–brain barrier transport of therapeutics via receptor-mediation. Pharm Res 2007;24:1759–1771.
    OpenUrlCrossRefPubMedWeb of Science
  20. 20.↵
    1. Dufès C,
    2. Al Robaian M,
    3. Somani S.
    Transferrin and the transferrin receptor for the targeted delivery of therapeutic agents to the brain and cancer cells. Ther Deliv 2013;4:629–640.
    OpenUrlCrossRefPubMed
  21. 21.↵
    1. Zhang P,
    2. Hu L,
    3. Yin Q,
    4. Feng L,
    5. Li Y.
    Transferrin-modified c [RGDfK]-paclitaxel loaded hybrid micelle for sequential blood-brain barrier penetration and glioma targeting therapy. Mol Pharm 2012;9:1590–1598.
    OpenUrlPubMed
  22. 22.↵
    1. Ying X,
    2. Wen H,
    3. Lu WL,
    4. Du J,
    5. Guo J,
    6. Tian W, et al.
    Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals. J Control Release 2010;141:183–192.
    OpenUrlCrossRefPubMedWeb of Science
  23. 23.↵
    1. Qin L,
    2. Wang CZ,
    3. Fan HJ,
    4. Zhang CJ,
    5. Zhang HW,
    6. Lv MH, et al.
    A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy. Oncol Lett 2014;8:2000–2006.
    OpenUrl
  24. 24.↵
    1. Porru M,
    2. Zappavigna S,
    3. Salzano G,
    4. Luce A,
    5. Stoppacciaro A,
    6. Balestrieri ML, et al.
    Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid. Oncotarget 2014;5:10446.
    OpenUrlPubMedWeb of Science
  25. 25.↵
    1. Chiu RY,
    2. Tsuji T,
    3. Wang SJ,
    4. Wang J,
    5. Liu CT,
    6. Kamei DT.
    Improving the systemic drug delivery efficacy of nanoparticles using a transferrin variant for targeting. J Control Release 2014;180:33–41.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Halbrooks PJ,
    2. Mason AB,
    3. Adams TE,
    4. Briggs SK,
    5. Everse SJ.
    The oxalate effect on release of iron from human serum transferrin explained. J Mol Biol 2004;339:217–226.
    OpenUrlPubMed
  27. 27.↵
    1. Yoon DJ,
    2. Kwan BH,
    3. Chao FC,
    4. Nicolaides TP,
    5. Phillips JJ,
    6. Lam GY, et al.
    Intratumoral therapy of glioblastoma multiforme using genetically engineered transferrin for drug delivery. Cancer Res 2010;70:4520–4527.
    OpenUrlAbstract/FREE Full Text
  28. 28.↵
    1. Pan W,
    2. Kastin AJ,
    3. Zankel TC,
    4. van Kerkhof P,
    5. Terasaki T,
    6. Bu G.
    Efficient transfer of receptor-associated protein (RA^P) across the blood-brain barrier. J Cell Sci 2004;117:5071–5078.
    OpenUrlAbstract/FREE Full Text
  29. 29.
    1. Bell RD,
    2. Sagare AP,
    3. Friedman AE,
    4. Bedi GS,
    5. Holtzman DM,
    6. Deane R, et al.
    Transport pathways for clearance of human Alzheimer's amyloid beta-peptide and apolipoproteins E and J in the mouse central nervous system. J Cereb Blood Flow Metab 2007;27:909–918.
    OpenUrlCrossRefPubMedWeb of Science
  30. 30.
    1. May P,
    2. Herz J,
    3. Bock H.
    Molecular mechanisms of lipoprotein receptor signalling. Cell Mol Life Sci 2005;62:2325–2338.
    OpenUrlCrossRefPubMedWeb of Science
  31. 31.↵
    1. Xin H,
    2. Jiang X,
    3. Gu J,
    4. Sha X,
    5. Chen L,
    6. Law K, et al.
    Angiopep-conjugated poly(ethylene glycol) -co-poly(ε-caprolactone) nanoparticles as dual-targeting drug delivery system for brain glioma. Biomaterials 2011;32:4293–4305.
    OpenUrl
  32. 32.
    1. Demeule M,
    2. Currie JC,
    3. Bertrand Y,
    4. Che C,
    5. Nguyen T,
    6. Regina A, et al.
    Involvement of the low-density lipoprotein receptor-related protein in the transcytosis of the brain delivery vector Angiopep-2. J Neurochem 2008;106:1534–1544.
    OpenUrlCrossRefPubMedWeb of Science
  33. 33.
    1. Ke W,
    2. Shao K,
    3. Huang R,
    4. Han L,
    5. Liu Y,
    6. Li J, et al.
    Gene delivery targeted to the brain using an Angiopep-conjugated polyethyleneglycol-modified polyamidoamine dendrimer. Biomaterials 2009;30:6976–6985.
    OpenUrlCrossRefPubMed
  34. 34.
    1. Shen J,
    2. Zhan C,
    3. Xie C,
    4. Meng Q,
    5. Gu B,
    6. Li C, et al.
    Poly (ethylene glycol)-block-poly (D, L-lactide acid) micelles anchored with angiopep-2 for brain-targeting delivery. J Drug Target 2011;19:197–203.
    OpenUrlPubMed
  35. 35.
    1. Ché C,
    2. Yang G,
    3. Thiot C,
    4. Lacoste MC,
    5. Currie JC,
    6. Demeule M, et al.
    New Angiopep-modified doxorubicin (ANG1007) and etoposide (ANG1009) chemotherapeutics with increased brain penetration. J Med Chem 2010;53:2814–2824.
    OpenUrlCrossRefPubMed
  36. 36.
    1. Shao K,
    2. Huang R,
    3. Li J,
    4. Han L,
    5. Ye L,
    6. Lou J, et al.
    Angiopep-2 modified PE-PEG based polymeric micelles for amphotericin B delivery targeted to the brain. J Control Release 2010;147:118–126.
    OpenUrlCrossRefPubMed
  37. 37.↵
    1. Huang S,
    2. Li J,
    3. Han L,
    4. Liu S,
    5. Ma H,
    6. Huang R, et al.
    Dual targeting effect of Angiopep-2-modified, DNA-loaded nanoparticles for glioma. Biomaterials 2011;32:6832–6838.
    OpenUrl
  38. 38.↵
    1. Gao H,
    2. Zhang S,
    3. Cao S,
    4. Yang Z,
    5. Pang Z,
    6. Jiang X.
    Angiopep-2 and activatable cell-penetrating peptide dual-functionalized nanoparticles for systemic glioma-targeting delivery. Mol Pharm 2014;11:2755–2763.
    OpenUrl
  39. 39.↵
    1. Ren J,
    2. Shen S,
    3. Wang D,
    4. Xi Z,
    5. Guo L,
    6. Pang Z, et al.
    The targeted delivery of anticancer drugs to brain glioma by PEGylated oxidized multi-walled carbon nanotubes modified with angiopep-2. Biomaterials 2012;33:3324–3333.
    OpenUrlCrossRefPubMedWeb of Science
  40. 40.↵
    1. Mei L,
    2. Zhang Q,
    3. Yang Y,
    4. He Q,
    5. Gao H.
    Angiopep-2 and activatable cell penetrating peptide dual modified nanoparticles for enhanced tumor targeting and penetrating. Int J Pharm 2014;474:95–102.
    OpenUrl
  41. 41.↵
    1. Ruan S,
    2. Yuan M,
    3. Zhang L,
    4. Hu G,
    5. Chen J,
    6. Cun X, et al.
    Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles. Biomaterials 2015;37:425–435.
    OpenUrl
  42. 42.↵
    1. Ying X,
    2. Wang Y,
    3. Liang J,
    4. Yue J,
    5. Xu C,
    6. Lu L, et al.
    Angiopep-Conjugated Electro-Responsive Hydrogel Nanoparticles: Therapeutic Potential for Epilepsy. Angew Chem Int Ed Engl 2014;53:12436–12440.
    OpenUrl
  43. 43.↵
    1. Suksrichavalit T,
    2. Prachayasittikul S,
    3. Isarankura-Na-Ayudhya C,
    4. Prachayasittikul V.
    Synthesis of a “clickable” Angiopep-conjugated p-coumaric acid for brain-targeted delivery. J Mater Sci 2014;49:8204–8213.
    OpenUrl
  44. 44.↵
    1. Chen GJ,
    2. Su YZ,
    3. Hsu C,
    4. Lo YL,
    5. Huang SJ,
    6. Ke JH, et al.
    Angiopep-pluronic F127-conjugated superparamagnetic iron oxide nanoparticles as nanotheranostic agents for BBB targeting. J Mater Chem B 2014;2:5666–5675.
    OpenUrl
  45. 45.↵
    1. Xuan S,
    2. Shin DH,
    3. Kim JS.
    Angiopep-2-conjugated liposomes encapsulating γ-secretase inhibitor for targeting glioblastoma stem cells. Journal of Pharmaceutical Investigation 2014;44:473–483.
    OpenUrl
  46. 46.↵
    1. Demeule M,
    2. Lachowicz JE,
    3. Yang G,
    4. Das S,
    5. Ché C,
    6. Tripathy S, et al.
    Utilization of the Angiopep platform to enable brain penetration of therapeutic mAbs or Antibody-Drug Conjugates for treatment of brain tumors. Cancer Res 2014;74:2657.
    OpenUrl
  47. 47.↵
    1. Wei X,
    2. Zhan C,
    3. Chen X,
    4. Hou J,
    5. Xie C,
    6. Lu W.
    Retro-inverso isomer of angiopep-2: a stable d-peptide ligand inspires brain-targeted drug delivery. Mol Pharm 2014;11:3261–3268.
    OpenUrl
  48. 48.↵
    1. Chen J,
    2. Li Y,
    3. Yu TS,
    4. McKay RM,
    5. Burns DK,
    6. Kernie SG, et al.
    A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 2012;488:522–526.
    OpenUrlCrossRefPubMedWeb of Science
  49. 49.
    1. Galderisi U,
    2. Cipollaro M,
    3. Giordano A.
    Stem cells and brain cancer. Cell Death Differ 2006;13:5–11.
    OpenUrlCrossRefPubMedWeb of Science
  50. 50.
    1. Singh SK,
    2. Hawkins C,
    3. Clarke ID,
    4. Squire JA,
    5. Bayani J,
    6. Hide T, et al.
    Identification of human brain tumour initiating cells. Nature 2004;432:396–401.
    OpenUrlCrossRefPubMedWeb of Science
  51. 51.↵
    1. Reguera-Nuñez E,
    2. Roca C,
    3. Hardy E,
    4. De la Fuente M,
    5. Csaba N,
    6. Garcia-Fuentes M.
    Implantable controlled release devices for BMP-7 delivery and suppression of glioblastoma initiating cells. Biomaterials 2014;35:2859–2867.
    OpenUrlCrossRefPubMed
  52. 52.↵
    1. Vecchio D,
    2. Daga A,
    3. Carra E,
    4. Marubbi D,
    5. Baio G,
    6. Neumaier CE, et al.
    Predictability, efficacy and safety of radiosensitization of glioblastoma-initiating cells by the ATM inhibitor KU-60019. Int J Cancer 2014;135:479–491.
    OpenUrlCrossRefPubMed
  53. 53.↵
    1. González-Gómez P,
    2. Anselmo NP,
    3. Mira H.
    BMPs as therapeutic targets and biomarkers in astrocytic glioma. Biomed Res Int 2014;2014:549742.
    OpenUrl
  54. 54.↵
    1. Kim M,
    2. Choe S.
    BMPs and their clinical potentials. BMB Rep 2011;44:619.
    OpenUrlCrossRefPubMedWeb of Science
  55. 55.↵
    1. Klose A,
    2. Waerzeggers Y,
    3. Monfared P,
    4. Vukicevic S,
    5. Kaijzel EL,
    6. Winkeler A, et al.
    Imaging bone morphogenetic protein 7 induced cell cycle arrest in experimental gliomas. Neoplasia 2011;13:276–285.
    OpenUrlPubMedWeb of Science
  56. 56.↵
    1. Nakano I,
    2. Saigusa K,
    3. Kornblum HI.
    BMPing off glioma stem cells. Cancer Cell 2008;13:3–4.
    OpenUrlCrossRefPubMed
  57. 57.↵
    1. Chirasani SR,
    2. Sternjak A,
    3. Wend P,
    4. Momma S,
    5. Campos B,
    6. Herrmann IM, et al.
    Bone morphogenetic protein-7 release from endogenous neural precursor cells suppresses the tumourigenicity of stem-like glioblastoma cells. Brain 2010;133:1961–1972.
    OpenUrlCrossRefPubMedWeb of Science
  58. 58.↵
    1. Piccirillo SG,
    2. Reynolds BA,
    3. Zanetti N,
    4. Lamorte G,
    5. Binda E,
    6. Broggi G, et al.
    Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature 2006;444:761–765.
    OpenUrlCrossRefPubMedWeb of Science
  59. 59.↵
    1. Wu Q,
    2. Yao J.
    BMP4, a new prognostic factor for glioma. World J Surg Oncol 2013;11:264.
    OpenUrlCrossRef
  60. 60.↵
    1. Liu B,
    2. Chen Q,
    3. Tian D,
    4. Wu L,
    5. Dong H,
    6. Wang J, et al.
    BMP4 reverses multidrug resistance through modulation of BCL-2 and GDNF in glioblastoma. Brain Res 2013;1507:115–124.
    OpenUrlCrossRefPubMed
  61. 61.↵
    1. Rahman M,
    2. Azari H,
    3. Deleyrolle L,
    4. Millette S,
    5. Zeng H,
    6. Reynolds BA.
    Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma. Future Oncol 2013;9:1389–1396.
    OpenUrl
  62. 62.↵
    1. Tate CM,
    2. Pallini R,
    3. Ricci-Vitiani L,
    4. Dowless M,
    5. Shiyanova T,
    6. D'Alessandris GQ, et al.
    A BMP7 variant inhibits the tumorigenic potential of glioblastoma stem-like cells. Cell Death Differ 2012;19:1644–1654.
    OpenUrlCrossRefPubMed
  63. 63.↵
    1. Liu C,
    2. Tian G,
    3. Tu Y,
    4. Fu J,
    5. Lan C,
    6. Wu N.
    Expression pattern and clinical prognostic relevance of bone morphogenetic protein-2 in human gliomas. Jpn J Clin Oncol 2009;39:625–631.
    OpenUrlCrossRefPubMedWeb of Science
  64. 64.↵
    1. Persano L,
    2. Pistollato F,
    3. Rampazzo E,
    4. Della Puppa A,
    5. Abbadi S,
    6. Frasson C, et al.
    BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression. Cell Death Dis 2012;3:e412.
  65. 65.↵
    1. Shin DH,
    2. Xuan S,
    3. Kim WY,
    4. Bae GU,
    5. Kim JS.
    CD133 antibody-conjugated immunoliposomes encapsulating gemcitabine for targeting glioblastoma stem cells. J Mater Chem B 2014;2:3771–3781.
    OpenUrl
  66. 66.↵
    1. Bai Y,
    2. Lathia JD,
    3. Zhang P,
    4. Flavahan W,
    5. Rich JN,
    6. Mattson MP.
    Molecular targeting of TRF2 suppresses the growth and tumorigenesis of glioblastoma stem cells. Glia 2014;62:1687–1698.
    OpenUrl
  67. 67.↵
    1. Shi L,
    2. Zhang S,
    3. Feng K,
    4. Wu F,
    5. Wan Y,
    6. Wang Z, et al.
    MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosis. Int J Oncol 2012;40:119–129.
    OpenUrlCrossRefPubMed
  68. 68.↵
    1. Shi L,
    2. Wan Y,
    3. Sun G,
    4. Zhang S,
    5. Wang Z,
    6. Zeng Y.
    miR-125b inhibitor may enhance the invasion-prevention activity of temozolomide in glioblastoma stem cells by targeting PIAS3. BioDrugs 2014;28:41–54.
    OpenUrl
  69. 69.↵
    1. Chen J,
    2. Fu X,
    3. Wan Y,
    4. Wang Z,
    5. Jiang D,
    6. Shi L.
    miR-125b inhibitor enhance the chemosensitivity of glioblastoma stem cells to temozolomide by targeting Bak1. Tumour Biol 2014;35:6293–6302.
    OpenUrl
  70. 70.↵
    1. Huang S,
    2. Shao K,
    3. Liu Y,
    4. Kuang Y,
    5. Li J,
    6. An S, et al.
    Tumor-targeting and microenvironment-responsive smart nanoparticles for combination therapy of antiangiogenesis and apoptosis. ACS Nano 2013;7:2860–2871.
    OpenUrlCrossRefPubMed
  71. 71.↵
    1. Stupp R,
    2. Hegi ME,
    3. Gorlia T,
    4. Erridge SC,
    5. Perry J,
    6. Hong YK, et al.
    Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol 2014;15:1100–1108.
    OpenUrlCrossRefPubMedWeb of Science
  72. 72.
    1. Roth P,
    2. Silginer M,
    3. Goodman SL,
    4. Hasenbach K,
    5. Thies S,
    6. Maurer G, et al.
    Integrin control of the transforming growth factor-β pathway in glioblastoma. Brain 2013;136:564–576.
    OpenUrlCrossRefPubMedWeb of Science
  73. 73.
    1. Barczyk M,
    2. Carracedo S,
    3. Gullberg D.
    Integrins. Cell Tissue Res 2010;339:269–280.
    OpenUrlCrossRefPubMedWeb of Science
  74. 74.↵
    1. Desgrosellier JS,
    2. Cheresh DA.
    Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer 2010;10:9–22.
    OpenUrlCrossRefPubMedWeb of Science
  75. 75.↵
    1. Kibria G,
    2. Hatakeyama H,
    3. Ohga N,
    4. Hida K,
    5. Harashima H.
    Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery. J Control Release 2011;153:141–148.
    OpenUrlCrossRefPubMedWeb of Science
  76. 76.↵
    1. Liu Y,
    2. Ran R,
    3. Chen J,
    4. Kuang Q,
    5. Tang J,
    6. Mei L, et al.
    Paclitaxel loaded liposomes decorated with a multifunctional tandem peptide for glioma targeting. Biomaterials 2014;35:4835–4847.
    OpenUrl
  77. 77.↵
    1. Gao H,
    2. Yang Z,
    3. Cao S,
    4. Xiong Y,
    5. Zhang S,
    6. Pang Z, et al.
    Tumor cells and neovasculature dual targeting delivery for glioblastoma treatment. Biomaterials 2014;35:2374–2382.
    OpenUrl
  78. 78.↵
    1. Reardon DA,
    2. Fink KL,
    3. Mikkelsen T,
    4. Cloughesy TF,
    5. O'Neill A,
    6. Plotkin S, et al.
    Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 2008;26:5610–5617.
    OpenUrlAbstract/FREE Full Text
  79. 79.
    1. Nabors LB,
    2. Mikkelsen T,
    3. Hegi ME,
    4. Ye X,
    5. Batchelor T,
    6. Lesser G, et al.
    A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). Cancer 2012;118:5601–5607.
    OpenUrlCrossRefPubMedWeb of Science
  80. 80.↵
    1. Gilbert MR,
    2. Kuhn J,
    3. Lamborn KR,
    4. Lieberman F,
    5. Wen PY,
    6. Mehta M, et al.
    Cilengitide in patients with recurrent glioblastoma: the results of NABTC 03-02, a phase II trial with measures of treatment delivery. J Neurooncol 2012;106:147–153.
    OpenUrlCrossRefPubMed
  81. 81.↵
    1. Eisele G,
    2. Wick A,
    3. Eisele AC,
    4. Clément PM,
    5. Tonn J,
    6. Tabatabai G, et al.
    Cilengitide treatment of newly diagnosed glioblastoma patients does not alter patterns of progression. J Neurooncol 2014;117:141–145.
    OpenUrlCrossRefPubMed
  82. 82.↵
    1. Padfield E,
    2. Ellis H,
    3. Kurian K.
    Current therapeutic advances targeting EGFR and EGFRvIII in glioblastoma. Front Oncol 2015;5:5.
    OpenUrlCrossRefPubMed
  83. 83.↵
    1. Carrasco-García E,
    2. Saceda M,
    3. Martínez-Lacaci I.
    Role of receptor tyrosine kinases and their ligands in glioblastoma. Cells 2014;3:199–235.
    OpenUrlCrossRef
  84. 84.↵
    1. Patel R,
    2. Y Leung H.
    Targeting the EGFR-family for therapy: biological challenges and clinical perspective. Curr Pharm Des 2012;18:2672–2679.
    OpenUrlCrossRefPubMed
  85. 85.↵
    1. Sampson JH,
    2. Aldape KD,
    3. Archer GE,
    4. Coan A,
    5. Desjardins A,
    6. Friedman AH, et al.
    Greater chemotherapy-induced lymphopenia enhances tumor-specific immune responses that eliminate EGFRvIII-expressing tumor cells in patients with glioblastoma. Neuro Oncol 2011;13:324–333.
    OpenUrlCrossRefPubMed
  86. 86.
    1. Cloughesy TF,
    2. Cavenee WK,
    3. Mischel PS.
    Glioblastoma: From molecular pathology to targeted treatment. Annu Rev Pathol 2014;9:1–25.
    OpenUrlCrossRefPubMed
  87. 87.↵
    1. Schuster J,
    2. Lai RK,
    3. Recht LD,
    4. Reardon DA,
    5. Paleologos NA,
    6. Groves MD, et al.
    A phase II, multicenter trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma: the ACT III study. Neuro Oncol 2015;17:854–61.
    OpenUrlCrossRefPubMed
  88. 88.↵
    1. Qaddoumi I,
    2. Kocak M,
    3. Panandiker ASP,
    4. Armstrong GT,
    5. Wetmore C,
    6. Crawford JR, et al.
    Phase II trial of erlotinib during and after radiotherapy in children with newly diagnosed high-grade gliomas. Front Oncol 2014;4:67.
    OpenUrlPubMed
  89. 89.↵
    1. Wen PY,
    2. Chang SM,
    3. Lamborn KR,
    4. Kuhn JG,
    5. Norden AD,
    6. Cloughesy TF, et al.
    Phase I/II study of erlotinib and temsirolimus for patients with recurrent malignant gliomas: North American Brain Tumor Consortium trial 04-02. Neuro Oncol 2014;16:567–578.
    OpenUrlCrossRefPubMed
  90. 90.↵
    1. Peereboom DM,
    2. Ahluwalia MS,
    3. Ye X,
    4. Supko JG,
    5. Hilderbrand SL,
    6. Phuphanich S, et al.
    NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme. Neuro Oncol 2013;15:490–496.
    OpenUrlCrossRefPubMed
  91. 91.↵
    1. Uhm JH,
    2. Ballman KV,
    3. Wu W,
    4. Giannini C,
    5. Krauss J,
    6. Buckner JC, et al.
    Phase II evaluation of gefitinib in patients with newly diagnosed Grade 4 astrocytoma: Mayo/North Central Cancer Treatment Group Study N0074. Int J Radiat Oncol Biol Phys 2011;80:347–353.
    OpenUrlCrossRefPubMed
  92. 92.↵
    1. Neyns B,
    2. Sadones J,
    3. Joosens E,
    4. Bouttens F,
    5. Verbeke L,
    6. Baurain JF, et al.
    Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 2009;20:1596–1603.
    OpenUrlCrossRefPubMedWeb of Science
  93. 93.↵
    1. Lv S,
    2. Teugels E,
    3. Sadones J,
    4. De Brakeleer S,
    5. Duerinck J,
    6. Du Four S, et al.
    Correlation of EGFR, IDH1 and PTEN status with the outcome of patients with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking monoclonal antibody cetuximab. Int J Oncol 2012;41:1029–1035.
    OpenUrlCrossRefPubMed
  94. 94.↵
    1. Wang Y,
    2. Pan L,
    3. Sheng XF,
    4. Chen S,
    5. Dai JZ.
    Nimotuzumab, a humanized monoclonal antibody specific for the EGFR, in combination with temozolomide and radiation therapy for newly diagnosed glioblastoma multiforme: First results in Chinese patients. Asia Pac J Clin Oncol 2014. [Epub ahead of print].
  95. 95.↵
    1. Westphal M,
    2. Heese O,
    3. Steinbach JP,
    4. Schnell O,
    5. Schackert G,
    6. Mehdorn M, et al.
    A randomised, open label phase III trial with nimotuzumab, an anti-epidermal growth factor receptor monoclonal antibody in the treatment of newly diagnosed adult glioblastoma. Eur J Cancer 2015;51:522–532.
    OpenUrl
  96. 96.↵
    1. Sampson JH,
    2. Heimberger AB,
    3. Archer GE,
    4. Aldape KD,
    5. Friedman AH,
    6. Friedman HS, et al.
    Immunologic escape after prolonged progression-free survival with epidermal growth factor receptor variant III peptide vaccination in patients with newly diagnosed glioblastoma. J Clin Oncol 2010;28:4722–4729.
    OpenUrlAbstract/FREE Full Text
  97. 97.
    1. Lai RK,
    2. Recht LD,
    3. Reardon DA,
    4. Paleologos N,
    5. Groves M,
    6. Rosenfeld MR, et al.
    IM-03: Long-term follow-up of ACT III: a phase II trial of rindopepimut (CDX-110) in newly diagnosed glioblastoma. Neuro Oncol 2011;13:ii34–ii40.
    OpenUrl
  98. 98.↵
    1. Swartz AM,
    2. Batich KA,
    3. Fecci PE,
    4. Sampson JH.
    Peptide vaccines for the treatment of glioblastoma. J Neurooncol 2015;123:433–440.
    OpenUrl
  99. 99.↵
    1. Ranza E,
    2. Mazzini G,
    3. Facoetti A,
    4. Nano R.
    In-vitro effects of the tyrosine kinase inhibitor imatinib on glioblastoma cell proliferation. J Neurooncol 2010;96:349–357.
    OpenUrlPubMed
  100. 100.↵
    1. Nazarenko I,
    2. Hede SM,
    3. He X,
    4. Hedrén A,
    5. Thompson J,
    6. Lindström MS, et al.
    PDGF and PDGF receptors in glioma. Ups J Med Sci 2012;117:99–112.
    OpenUrlCrossRefPubMed
  101. 101.↵
    1. Ehnman M,
    2. Östman A.
    Therapeutic targeting of platelet-derived growth factor receptors in solid tumors. Expert Opin Investig Drugs 2014;23:211–226.
    OpenUrl
  102. 102.↵
    1. Holdhoff M,
    2. Supko JG,
    3. Gallia GL,
    4. Hann CL,
    5. Bonekamp D,
    6. Ye X, et al.
    Intratumoral concentrations of imatinib after oral administration in patients with glioblastoma multiforme. J Neurooncol 2010;97:241–245.
    OpenUrlCrossRefPubMed
  103. 103.↵
    1. Dong Y,
    2. Han Q,
    3. Zou Y,
    4. Deng Z,
    5. Lu X,
    6. Wang X, et al.
    Long-term exposure to imatinib reduced cancer stem cell ability through induction of cell differentiation via activation of MAPK signaling in glioblastoma cells. Mol Cell Biochem 2012;370:89–102.
    OpenUrlPubMed
  104. 104.↵
    1. Dong Y,
    2. Jia L,
    3. Wang X,
    4. Tan X,
    5. Xu J,
    6. Deng Z, et al.
    Selective inhibition of PDGFR by imatinib elicits the sustained activation of ERK and downstream receptor signaling in malignant glioma cells. Int J Oncol 2011;38:555.
    OpenUrlCrossRefPubMed
  105. 105.↵
    1. Dresemann G,
    2. Weller M,
    3. Rosenthal MA,
    4. Wedding U,
    5. Wagner W,
    6. Engel E, et al.
    Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. J Neurooncol 2010;96:393–402.
    OpenUrlCrossRefPubMed
  106. 106.↵
    1. Reardon DA,
    2. Dresemann G,
    3. Taillibert S,
    4. Campone M,
    5. van den Bent M,
    6. Clement P, et al.
    Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma. Br J Cancer 2009;101:1995–2004.
    OpenUrlCrossRefPubMedWeb of Science
  107. 107.↵
    1. Reardon DA,
    2. Turner S,
    3. Peters KB,
    4. Desjardins A,
    5. Gururangan S,
    6. Sampson JH, et al.
    A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma. J Natl Compr Canc Netw 2011;9:414–427.
    OpenUrlAbstract/FREE Full Text
  108. 108.↵
    1. Balana C,
    2. Gil MJ,
    3. Perez P,
    4. Reynes G,
    5. Gallego O,
    6. Ribalta T, et al.
    Sunitinib administered prior to radiotherapy in patients with non-resectable glioblastoma: results of a phase II study. Target Oncol 2014;9:321–329.
    OpenUrlCrossRefPubMed
  109. 109.↵
    1. Hutterer M,
    2. Nowosielski M,
    3. Haybaeck J,
    4. Embacher S,
    5. Stockhammer F,
    6. Gotwald T, et al.
    A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07). Neuro Oncol 2014;16:92–102.
    OpenUrlCrossRefPubMed
  110. 110.↵
    1. Pan E,
    2. Yu D,
    3. Yue B,
    4. Potthast L,
    5. Chowdhary S,
    6. Smith P, et al.
    A prospective phase II single-institution trial of sunitinib for recurrent malignant glioma. J Neurooncol 2012;110:111–118.
    OpenUrlCrossRefPubMed
  111. 111.
    1. Kreisl TN,
    2. Smith P,
    3. Sul J,
    4. Salgado C,
    5. Iwamoto FM,
    6. Shih JH, et al.
    Continuous daily sunitinib for recurrent glioblastoma. J Neurooncol 2013;111:41–48.
    OpenUrlCrossRefPubMed
  112. 112.↵
    1. Reardon DA,
    2. Vredenburgh JJ,
    3. Coan A,
    4. Desjardins A,
    5. Peters KB,
    6. Gururangan S, et al.
    Phase I study of sunitinib and irinotecan for patients with recurrent malignant glioma. J Neurooncol 2011;105:621–627.
    OpenUrlCrossRefPubMed
  113. 113.↵
    1. Batchelor TT,
    2. Duda DG,
    3. di Tomaso E,
    4. Ancukiewicz M,
    5. Plotkin SR,
    6. Gerstner E, et al.
    Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. J Clin Oncol 2010;28:2817–2823
    OpenUrlAbstract/FREE Full Text
  114. 114.↵
    1. Gerstner ER,
    2. Emblem KE,
    3. Chi AS,
    4. Eichler AF,
    5. Hochberg F,
    6. Drappatz J, et al.
    Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma. J Clin Oncol 2012;30:abstr 2009.
  115. 115.↵
    1. Batchelor TT,
    2. Gerstner ER,
    3. Emblem KE,
    4. Duda DG,
    5. Kalpathy-Cramer J,
    6. Snuderl M, et al.
    Improved tumor oxygenation and survival in glioblastoma patients who show increased blood perfusion after cediranib and chemoradiation. Proc Natl Acad Sci U S A 2013;110:19059–19064.
    OpenUrlAbstract/FREE Full Text
  116. 116.↵
    1. Batchelor TT,
    2. Mulholland P,
    3. Neyns B,
    4. Nabors LB,
    5. Campone M,
    6. Wick A, et al.
    Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 2013;31:3212–3218.
    OpenUrlAbstract/FREE Full Text
  117. 117.↵
    1. Pinho MC,
    2. Polaskova P,
    3. Kalpathy-Cramer J,
    4. Jennings D,
    5. Emblem KE,
    6. Jain RK, et al.
    Low incidence of pseudoprogression by imaging in newly diagnosed glioblastoma patients treated with cediranib in combination with chemoradiation. Oncologist 2014;19:75–81.
    OpenUrlAbstract/FREE Full Text
  118. 118.↵
    1. Kratzsch T,
    2. Gruenwald V,
    3. Vajkoczy P,
    4. Kuhn SA.
    Use of axitinib, a new-generation tyrosine kinase inhibitor, to decrease glioblastoma growth despite primary resistance to the VEGF-antibody bevacizumab. J Clin Oncol 2013;31:abstr 2077.
  119. 119.↵
    1. Lu L,
    2. Saha D,
    3. Martuza RL,
    4. Rabkin SD,
    5. Wakimoto H.
    Single agent efficacy of the VEGFR kinase inhibitor axitinib in preclinical models of glioblastoma. J Neurooncol 2015;121:91–100.
    OpenUrlPubMed
  120. 120.↵
    1. Duerinck J,
    2. Du Four S,
    3. Bouttens F,
    4. Verschaeve V,
    5. Everaert H,
    6. De Raedt S, et al.
    O10.07 Randomezed phase II study of axitinib vs. standard of care in patients with recurrent glioblastoma. Neuro Oncol 2014;16:ii24–ii25.
    OpenUrlCrossRef
  121. 121.↵
    1. Goldlust SA,
    2. Cavaliere R,
    3. Newton HB,
    4. Hsu M,
    5. DeAngelis LM,
    6. Batchelor TT, et al.
    Bevacizumab for glioblastoma refractory to vascular endothelial growth factor receptor inhibitors. J Neurooncol 2012;107:407–411.
    OpenUrlCrossRefPubMed
  122. 122.↵
    1. Gilbert MR,
    2. Dignam JJ,
    3. Armstrong TS,
    4. Wefel JS,
    5. Blumenthal DT,
    6. Vogelbaum MA, et al.
    A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 2014;370:699–708.
    OpenUrlCrossRefPubMedWeb of Science
  123. 123.↵
    1. Taal W,
    2. Oosterkamp HM,
    3. Walenkamp AM,
    4. Dubbink HJ,
    5. Beerepoot LV,
    6. Hanse MC, et al.
    Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 2014;15:943–953.
    OpenUrlCrossRefPubMedWeb of Science
  124. 124.↵
    1. Taal W,
    2. Oosterkamp HM,
    3. Walenkamp AM,
    4. Dubbink HJ,
    5. Beerepoot LV,
    6. Hanse M, et al.
    O10.05 Final analysis of the BELOB trial (a randomised phase II study on bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma) and first radiology review results. Neuro Oncol 2014;16:ii24.
    OpenUrlCrossRef
  125. 125.↵
    1. Taal W,
    2. Enting R,
    3. Taphoorn M,
    4. Smits M,
    5. Dubbink H,
    6. Beerepoot L, et al.
    AT-55 Final analysis of the BELOB trial (a randomised phase II study on bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma) and first radiology review results. Neuro Oncol 2014;16:v20–v21.
    OpenUrlCrossRef
  126. 126.↵
    1. Carlson JA,
    2. Reddy K,
    3. Gaspar LE,
    4. Ney D,
    5. Kavanagh BD,
    6. Damek D, et al.
    Hypofractionated-intensity modulated radiation therapy (Hypo-IMRT) and temozolomide (TMZ) with and without bevacizumab (BEV) for glioblastoma multiforme (GBM): a comparison of 2 prospective phase 2 trials. Int J Radiat Oncol Biol Phys 2014;90:S284.
    OpenUrl
  127. 127.
    1. Herrlinger U,
    2. Schäfer N,
    3. Steinbach JP,
    4. Weyerbrock A,
    5. Hau P,
    6. Goldbrunner R, et al.
    O10.04 The randomised, multicenter GLARIUS trial in vestigating bevacizumab/ irinotecan vs standard temozolomide in newly diagnosed, MGMT-non-methylated glioblastoma patients: final survival results and quality of life. Neuro Oncol 2014;16:ii23–ii24.
    OpenUrlCrossRef
  128. 128.↵
    1. Chauffert B,
    2. Feuvret L,
    3. Bonnetain F,
    4. Taillandier L,
    5. Frappaz D,
    6. Taillia H, et al.
    Randomized phase II trial of irinotecan and bevacizumab as neo-adjuvant and adjuvant to temozolomide-based chemoradiation compared to temozolomide-chemoradiation for unresectable glioblastoma: final results of the TEMAVIR study from ANOCEF. Ann Oncol 2014;25:1442–1447.
    OpenUrlCrossRefPubMedWeb of Science
  129. 129.↵
    1. Reardon DA,
    2. Desjardins A,
    3. Peters KB,
    4. Gururangan S,
    5. Sampson JH,
    6. McLendon RE, et al.
    Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naive, recurrent glioblastoma. J Neurooncol 2012;107:155–164.
    OpenUrlCrossRefPubMed
  130. 130.↵
    1. Clarke JL,
    2. Molinaro AM,
    3. Phillips JJ,
    4. Butowski NA,
    5. Chang SM,
    6. Perry A, et al.
    A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro Oncol 2014;16:984–990.
    OpenUrlCrossRefPubMed
  131. 131.↵
    1. Farias-Eisner G,
    2. Bank AM,
    3. Hwang BY,
    4. Appelboom G,
    5. Piazza MA,
    6. Bruce SS, et al.
    Glioblastoma biomarkers from bench to bedside: advances and challenges. Br J Neurosurg 2012;26:189–194.
    OpenUrlCrossRefPubMed
  132. 132.↵
    1. Hermansen SK,
    2. Kristensen BW.
    MicroRNA biomarkers in glioblastoma. J Neurooncol 2013;114:13–23.
    OpenUrlCrossRefPubMed
  133. 133.↵
    1. Qian X,
    2. Ren Y,
    3. Shi Z,
    4. Long L,
    5. Pu P,
    6. Sheng J, et al.
    Sequence-dependent synergistic inhibition of human glioma cell lines by combined temozolomide and miR-21 inhibitor gene therapy. Mol Pharm 2012;9:2636–2645.
    OpenUrlCrossRefPubMed
  134. 134.↵
    1. Chan JA,
    2. Krichevsky AM,
    3. Kosik KS.
    MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res 2005;65:6029–6033.
    OpenUrlAbstract/FREE Full Text
  135. 135.↵
    1. Ciafrè SA,
    2. Galardi S,
    3. Mangiola A,
    4. Ferracin M,
    5. Liu CG,
    6. Sabatino G, et al.
    Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun 2005;334:1351–1358.
    OpenUrlCrossRefPubMedWeb of Science
  136. 136.
    1. Gaur AB,
    2. Holbeck SL,
    3. Colburn NH,
    4. Israel MA.
    Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo. Neuro Oncol 2011;13:580–590.
    OpenUrlCrossRefPubMed
  137. 137.↵
    1. Lawler S,
    2. Chiocca EA.
    Emerging functions of microRNAs in glioblastoma. J Neurooncol 2009;92:297–306.
    OpenUrlCrossRefPubMed
  138. 138.↵
    1. Chao TF,
    2. Xiong HH,
    3. Liu W,
    4. Chen Y,
    5. Zhang JX.
    MiR-21 mediates the radiation resistance of glioblastoma cells by regulating PDCD4 and hMSH2. J Huazhong Univ Sci Technolog Med Sci 2013;33:525–529.
    OpenUrl
  139. 139.
    1. Gwak HS,
    2. Kim TH,
    3. Jo GH,
    4. Kim YJ,
    5. Kwak HJ,
    6. Kim JH, et al.
    Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PLoS One 2012;7:e47449.
  140. 140.↵
    1. Liu J,
    2. Zhu H,
    3. Yang X,
    4. Ge Y,
    5. Zhang C,
    6. Qin Q, et al.
    MicroRNA-21 is a novel promising target in cancer radiation therapy. Tumour Biol 2014;35:3975–3979.
    OpenUrlPubMed
  141. 141.↵
    1. Ren Y,
    2. Kang CS,
    3. Yuan XB,
    4. Zhou X,
    5. Xu P,
    6. Han L, et al.
    Co-delivery of as-miR-21 and 5-FU by poly (amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed 2010;21:303–314.
    OpenUrlCrossRefPubMedWeb of Science
  142. 142.↵
    1. Qian X,
    2. Long L,
    3. Shi Z,
    4. Liu C,
    5. Qiu M,
    6. Sheng J, et al.
    Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma. Biomaterials 2014;35:2322–2335.
    OpenUrlCrossRefPubMedWeb of Science
  143. 143.↵
    1. Costa PM,
    2. Cardoso AL,
    3. Custódia C,
    4. Cunha P,
    5. Pereira de Almeida L,
    6. Pedroso de Lima MC.
    MiRNA-21 silencing mediated by tumor-targeted nanoparticles combined with sunitinib: A new multimodal gene therapy approach for glioblastoma. J Control Release 2015;207:31–39.
    OpenUrl
  144. 144.↵
    1. She X,
    2. Yu Z,
    3. Cui Y,
    4. Lei Q,
    5. Wang Z,
    6. Xu G, et al.
    miR-181 subunits enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeleton remodeling in glioblastoma cells. Med Oncol 2014;31:1–10.
    OpenUrl
  145. 145.↵
    1. Wang XF,
    2. Shi ZM,
    3. Wang XR,
    4. Cao L,
    5. Wang YY,
    6. Zhang JX, et al.
    MiR-181d acts as a tumor suppressor in glioma by targeting K-ras and Bcl-2. J Cancer Res Clin Oncol 2012;138:573–584.
    OpenUrlPubMed
  146. 146.↵
    1. Wang J,
    2. Sai K,
    3. Chen FR,
    4. Chen ZP.
    miR-181b modulates glioma cell sensitivity to temozolomide by targeting MEK1. Cancer Chemother Pharmacol 2013;72:147–158.
    OpenUrlCrossRefPubMed
  147. 147.↵
    1. Zhang W,
    2. Zhang J,
    3. Hoadley K,
    4. Kushwaha D,
    5. Ramakrishnan V,
    6. Li S, et al.
    miR-181d: a predictive glioblastoma biomarker that downregulates MGMT expression. Neuro Oncol 2012;14:712–719.
    OpenUrlCrossRefPubMed
  148. 148.↵
    1. Yang ZZ,
    2. Li JQ,
    3. Wang ZZ,
    4. Dong DW,
    5. Qi XR.
    Tumor-targeting dual peptides-modified cationic liposomes for delivery of siRNA and docetaxel to gliomas. Biomaterials 2014;35:5226–5239.
    OpenUrlCrossRefPubMedWeb of Science
  149. 149.↵
    1. Genovese G,
    2. Ergun A,
    3. Shukla SA,
    4. Campos B,
    5. Hanna J,
    6. Ghosh P, et al.
    microRNA regulatory network inference identifies miR-34a as a novel regulator of TGF-ß signaling in glioblastoma. Cancer Discov 2012;2:736–749.
    OpenUrlAbstract/FREE Full Text
  150. 150.↵
    1. Zhang M,
    2. Kleber S,
    3. Röhrich M,
    4. Timke C,
    5. Han N,
    6. Tuettenberg J, et al.
    Blockade of TGF-ß signaling by the TGFßR-I kinase inhibitor LY2109761 enhances radiation response and prolongs survival in glioblastoma. Cancer Res 2011;71:7155–7167.
    OpenUrlAbstract/FREE Full Text
  151. 151.↵
    1. Carra E,
    2. Barbieri F,
    3. Marubbi D,
    4. Pattarozzi A,
    5. Favoni RE,
    6. Florio T, et al.
    Sorafenib selectively depletes human glioblastoma tumor-initiating cells from primary cultures. Cell Cycle 2013;12:491–500.
    OpenUrlPubMed
  152. 152.↵
    1. Aldea MD,
    2. Petrushev B,
    3. Soritau O,
    4. Tomuleasa CI,
    5. Berindan-Neagoe I,
    6. Filip AG, et al.
    Metformin plus sorafenib highly impacts temozolomideresistant glioblastoma stem-like cells. J BUON 2014;19:502–511.
    OpenUrl
  153. 153.↵
    1. Young JS,
    2. Morshed RA,
    3. Kim JW,
    4. Balyasnikova IV,
    5. Ahmed AU,
    6. Lesniak MS.
    Advances in stem cells, induced pluripotent stem cells, and engineered cells: delivery vehicles for anti-glioma therapy. Expert Opin Drug Deliv 2014;11:1733–1746.
    OpenUrl
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Cancer Biology and Medicine: 12 (3)
Cancer Biology & Medicine
Vol. 12, Issue 3
1 Sep 2015
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Development of targeted therapies in treatment of glioblastoma
Yuan-Yuan Xu, Pei Gao, Ying Sun, You-Rong Duan
Cancer Biology & Medicine Sep 2015, 12 (3) 223-237; DOI: 10.7497/j.issn.2095-3941.2015.0020

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Development of targeted therapies in treatment of glioblastoma
Yuan-Yuan Xu, Pei Gao, Ying Sun, You-Rong Duan
Cancer Biology & Medicine Sep 2015, 12 (3) 223-237; DOI: 10.7497/j.issn.2095-3941.2015.0020
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Keywords

  • Glioblastoma (GBM)
  • targeted therapy
  • blood-brain barrier (BBB)
  • clinical trial

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